The goals of these studies are to determine the structure and function of intermediate filaments and their associated proteins in mammalian cells. Intermediate filaments are major cytoskeletal structures and their constituent proteins vary in a cell type specific fashion. The specific aims of the proposed research are to determine the mechanisms underlying the assembly of intermediate filament networks, the interactions of intermediate filaments with microtubules, and the regulation of their dynamic and motile properties. The techniques employed in these studies include light and electron microscopy, single cell microinjection methods, biochemical characterization of proteins, and the cloning and transfection of wild type and mutant cDNAs in cultured mammalian cells. The results of these studies are related to human health as it has been demonstrated that there are many diseases linked to mutations in the structural proteins comprising intermediate filaments and there are other diseases in which abnormal accumulations of intermediate filaments are a pathological hallmark of disease. The latter include the formation of Mallory bodies in alcoholic liver disease and Lewy bodies in Parkinson's disease.